Most research regarding the functional properties of the endogenous opiate-like neuropeptides has been directed at their analgesic effects. Work in our laboratory indicates that beta-endorphin also produces a broad spectrum of dose-related behavioral and physiological effects, including: (1) a profound state of immobilization; (2) signs of opiate withdrawal, i.e., wet-dog shakes; and (3) behavioral hyperactivity consisting of enhanced locomotion and stereotypy similar to that induced by amphetamine. The purpose of the proposed research is: (1) to characterize further the behavioral response pattern produced by acute and repeated administration of the endogenous opiate-like neuropeptides and synthetic opiates in rats. Initially, studies will focus on the effects produced by beta-endorphin, methadone and etonitazene; (2) to determine the role of monoamine systems and mechanisms in these behaviors with the use of neurotoxic agents and other pharmacological manipulations; and (3) to elucidate the relative contribution of various brain structures by discrete microinjection of beta-endorphin, opiates and naloxone. The proposed studies may provide for a more complete understanding of: (1) the role of the opiate-like neuropeptides in behavioral regulation; (2) the euphorogenic properties of opiates and the mechanisms underlying withdrawal and physical dependence; and (3) the possible role of these neuropeptides in clinical psychopathology.